Action Points

Explain that a U.K. study found that neither overall survival nor progression-free survival improved with the addition of cetuximab to standard chemotherapy in treatment-naive patients with advanced colon cancer.

Patients with KRAS wild-type tumors, who had been expected to benefit most from cetuximab, did not show benefit for either the primary or secondary endpoints of survival.

In a phase III clinical trial, overall survival was the same whether or not cetuximab was added to chemotherapy with oxaliplatin (Eloxatin) and a fluoropyrimidine, according to Richard Kaplan, MD, of the Clinical Trials Unit of the Medical Research Council (MRC) of the United Kingdom, and colleagues.

The researchers found the same result, regardless of whether or not the tumor cells had several common mutations, they said online in The Lancet.

Adding the drug also had no significant effect on progression-free survival (PFS), although there was a modest but significant increase in the rate of response, the researchers reported.

The results are "unexpected," according to Madeleine Hewish, MD, and David Cunningham, MD, both of the Royal Marsden Hospital in London.

Earlier studies had suggested a benefit in patients who did not respond to chemotherapy, and in those treated with a combination of cetuximab and the topoisomerase inhibitor irinotecan (Camptosar), they noted in an accompanying commentary in The Lancet.

Cetuximab targets the epidermal growth factor receptor and earlier research suggested that in colorectal cancer, the benefit was restricted to patients whose tumors did not have KRAS mutation, Kaplan and colleagues noted.

The researchers wanted to see if the drug would be useful as an addition to chemotherapy in patients with advanced colorectal cancer who had not yet been treated.

The MRC COIN trial, with 1,630 patients, had three arms, two comparing chemotherapy with and without cetuximab and a third testing intermittent chemotherapy. Results from the third arm are being reported elsewhere, they noted.

All told, 815 patients were assigned to chemotherapy alone and another 815 received chemo plus cetuximab, they reported. The follow up showed:

Among patients whose tumors lacked the KRAS mutation, overall survival did not differ. The median survival was 17.9 months in the control group compared with 17 months in the cetuximab group.

The drug also did not delay progression. Patients in both the control group and the cetuximab group had PFS of 8.6 months.

The overall response rate increased from 57% with chemotherapy alone to 64% when cetuximab was added, a difference that was significant at P=0.049.

Regardless of the treatment, overall survival did differ by mutation, Kaplan and colleagues reported, from a high of 20.1 months for those with wild-type tumors, through 14.4 months for those with KRAS mutations, to 8.8 months for those with a BRAF mutation.

"No benefit could be shown with the addition of cetuximab to oxaliplatin-based chemotherapy," the researchers concluded.

At least part of the reason for the outcome might be overlapping gastrointestinal toxicities between cetuximab and other drugs in the regimens, they noted.

However, they argued, "the trial showed the powerful effect of the presence of specific mutations in the tumor on prognosis and this should influence future clinical trials in bowel cancer."

The study had support from Cancer Research U.K., Cancer Research Wales, the U.K. Medical Research Council, and Merck KGgA. Kaplan is an employee of the MRC.